Dihydromyricetin promotes GLP-1 secretion to improve insulin resistance via "gut microbiota-CDCA"

Dihydromyricetin (DHM) is a polyphenolic phytochemical found mainly in plants such as Ampelopsis grossedentata, which has beneficial effects on insulin resistance. However, the specific mechanism has not been clarified. In this study, C57BL/6 mice were exposed to a high-fat diet (HFD) for eight weeks. DHM could improve insulin resistance via enhancing the incretin effect. DHM increased serum GLP-1 by improving intestinal GLP-1 secretion and inhibiting GLP-1 decomposition, associated with the alteration of intestinal intraepithelial lymphocytes (IELs) proportions and decreased expression of CD26 in IELs and TCR{beta}+ CD8{beta}+ IELs in HFD-induced mice. Meanwhile, DHM could ameliorate GLP-1 level and insulin resistance by modulation of gut microbiota and the metabolites, particularly the regulation of intestinal bile acid CDCA content, followed by the inhibition of FXR expression in intestinal L cells as well as increased Gcg mRNA expression and the secretion of GLP-1. These findings clarify the role of the "gut microbiota-CDCA" pathway in the improvement of intestinal GLP-1 levels in HFD-induced mice by DHM administration, providing a new pharmacological target for the prevention of insulin resistance.